Obsessive-compulsive neurosis is "a neurotic disorder characterized by the presence of recurrent ideas and fantasies and repetitive impulses or actions that the patient recognizes as morbid and toward which he feels a strong inner resistance." (Merck Manual, 15th Ed., p. 1505).
Tourettes' syndrome is a multiple tic disorder which "begins in childhood with simple tics but progresses to multiple, complex movements including respiratory and vocal tics." (Merck Manual, 15th Ed., p. 1419).
Pimozide, a known anti-psychotic has been suggested for use in treating both obsessive-compulsive neurosis and Tourettes' syndrome. However, it has been found that where sufficiently large amounts of pimozide are employed to produce a beneficial effect in treating the above disorders, significant side effects may be encountered. Thus, where amounts of pimozide greater than 0.04 mg/kg/day or greater than 2 mg per day, are employed over prolonged periods, tardive dyskinesia may result. Other side effects as a result of using pimozide include neuroleptic malignant syndrome (NMS), extra-pyramidal reactions, neuromuscular reactions, impaired cognition and anticholinergic side effects.
Accordingly, a need exists for a drug or combination of drugs which may be used to treat obsessive-compulsive neurosis, and motor and phonic tics associated with Tourettes' syndrome which will not produce the untoward side effects normally resulting from use of therapeutic dosages of pimozide.
U.S. Pat. Nos. 4,046,889 and 4,105,776 to Ondetti et al. disclose proline derivatives, including captopril, which are angiotensin converting enzyme (ACE) inhibitors useful for treating hypertension.
U.S. Pat. No. 4,337,201 to Petrillo discloses phosphinylalkanoyl substituted prolines, including fosinopril, which are ACE inhibitors useful for treating hypertension.
U.S. Pat. No. 4,374,829 discloses carboxyalkyl dipeptide derivatives, including enalapril, which are ACE inhibitors useful for treating hypertension.
U.S. Pat. No. 4,452,790 to Karanewsky et al. discloses phosphonate substituted amino or imino acids and salts thereof and covers (S)-1-[6-amino-2-[[hydroxy(4-phenylbutyl)phosphinyl]-oxy]-1-oxohexyl]-L-pr oline (SQ 29,852, ceranapril). These compounds are ACE inhibitors useful in treating hypertension.
U.S. Pat. No. 4,316,906 to Ondetti et al. discloses ether and thioether mercaptoacyl prolines which are ACE inhibitors useful in treating hypertension. This Ondetti et al. patent covers zofenopril.
It is now believed that angiotensin converting enzyme inhibitors, especially mercapto containing ACE inhibitors such as captopril and zofenopril, when employed in combination with dopaminergic receptor blockers, such as pimozide, for treating obsessive-compulsive neurosis and Tourettes' syndrome are capable of reducing and, in some cases, preventing side effects resulting from use of the dopaminergic receptor blocker.